Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1

Yufeng Zhou , et al.  Nat Med. 10(2010)

Speaker: Chia-Lun Tsai(蔡佳倫)                           Time: 14:10-15:00, Dec. 29, 2010

Commentator: Dr. Chi-Chang Shieh (謝奇璋 醫師)           Place: Room 601

Abstract

Gastrointestinal laminar propria dendritic cells (LPDCs) can use innate pattern-recognition molecule such as the C-type lectin receptors (CLRs) SIGNR1 to recognize complex glycan structures of pathogens via its C-type (calcium dependent) carbohydrate-recognition domains (CRDs) for endocytosis of pathogens. The authors hypothesis that the sugar-modified antigen Man51-BSA , which is similar to mannosylated stuctures of pathogen ligand, may target LPDC C-type lectin receptors (CLRs) SIGNR1 to induce oral tolerance in food-induced systemic anaphylaxis . The authors found BSA-sensitized mice pretreated with Man51-BSA , but not with BSA , was able to decrease the severity of anaphylaxis after challenged with BSA in this murine model of food-induced anaphylaxis . To analysis the role of LPDC in this murine model of glycosylated BSA-induced anaphylaxis, naive mice were treated with oral FITC-labeled Man51-BSA or FITC-labeled BSA. It was found that LPDCs (CLRs) SIGNR1 can be selected in the CD11c+CD11b+ DC subset that bound with FITC-labeled Man51-BSA or FITC-labeled BSA in flow cytometry analyses. To examine the cytokines production in lamina propria CD11c+ DCs stimulated with BSA or Man51-BSA, T cells cultured with Man51-BSA-pulsed or BSA-pulsed LPDCs, and there was a significantly increased con­centrations of IL-10 and IFN-γ in Man51-BSA co-culture condition.TheConclusion is Man51-BSA by the C-type lectin SIGNR1 on lamina propria DCs unleashes a cascade of tolerogenic events involving secretion of IL-10, which leads to the generation of Tr1 cells in mesenteric lymph nodes. CCR7 expression may direct lamina propria DCs to mesenteric lymph nodes to encounter T cells. Upon differentiation, Tr1 cells secrete IL-10 and interferon-γ (IFN-γ) to prevent systemic anaphylaxis and promote oral tolerance in response to food allergens.

References

1.  A C-type lectin on dendritic cells that unveils manyaspects of dendritic cell biology. Teunis B. H. et al. Journal of Leukocyte Biology 71(2002)

•  Anatomical basis of tolerance and immunity to intestinal antigens. Nat. Rev. Mowat, A.M, et al . Immunol. 3(2003).